| Object:Diabetic kidney disease (DKD) is one of the most important microangiopathies of diabetes mellitus (DM). In addition, a low degree of inflammation is increasingly considered to the major mechanisms which contribute to the development of glomerular damage in diabetes. Proteinuria is the most important presentation of DKD. Podocyte injury causes not only the destruction of the glomerular filtration barrier, but also the formation of proteinuria, leading to glomerular sclerosis. Monocyte chemoattractant protein-1(MCP-1) is a potent chemokine, which can induce the aggregation of various inflammatory cells, especially monocytes. The existed researches showed that MCP-1plays a key role in the process of proteinuria.Pioglitazone, one of the thiazolidinediones(TZDs), which plays a role in renoprotection through a variety of ways, including regulating glucose and lipid metabolism, improving insulin resistance, improving inflammation and atherosclerosis. Cordyceps sinensis (Berk.) Sacc is a kind of valuable, traditional and invigorating the kidney herb in our country. It is confirmed that Cordyceps sinensis (Berk.)Sacc has the effect of reinforcing on kidneys and lungs, improving fragile conditions, and assisting pneuma. Previous studies found that CS has some therapeutic effects on DKD, but the exact mechanism is not clear.In this study, Type1diabetic rat model was established by intravenous injection of streptozocin (STZ). Cordyceps sinensis cultivated by artificial fermentation and Pioglitazone were applied to the diabetic rats. The expression of MCP-1、nephrin and desmin of the kidneys were detected by the use of pathological morphology and molecular biology. Our aim was to assess the potential relevance of the MCP-1and nephrin in the occurrence and development of diabetic kidney disease. At the same time, the renal protective mechanism of Cordyceps sinensis cultivated by artificial fermentation and Pioglitazone were investigated in this study.Materials and Methods:90eight-week male SD rats were divided into two groups randomly:10normal control rats (group CON) and80experimental rats. The DM rat models were made by intravenous injection of STZ(45mg/kg).Then, they were randomly assigned into six groups, including control group(group CON),diabetes group(group DM), small-dose CS group(group L,0.6g/kg/d), medium-dose CS group(group M,2.5g/kg/d),large-dose CS group(group H,5g/kg/d), PIO treatment group(group PIO,4mg/kg/d).Eight weeks later, renal function,total cholesterol,urine albumin were evaluated. The Pathological changes of the kidneys were studied by Light and Electron Microscope. The expression of MCP-1、nephrin、desmin were detected by immunohistochemistry and immunofluorescene. The mRNA expressions of nephrin in kidney tissue was assessed by reverse transcription-polymerase chain reaction(RT-PCR).Results:1.In group DM, focal segmental glomerulosclerosis,fibrosis,widespread deposition of glycogen granules in proximal tubular epithelial cells(PTEC) were showed by light microscope. Irregular thicking of glomerular basement membrane, mesangial expansion and fusion of foot processes were observed by electron microscope. The changes mentioned above were relieved to some extent in the groups treated with PIO or CS. Furthermore, the effects in group H and PIO were better than those in groups L or M (P<0.05).2. Comparing with the control group, the expression of MCP-1was remarkably increased in group DM.The expression of MCP-1was obviously decreased in PIO or CS treatment groups than in group DM. MCP-1were significantly lower in group H and PIO than those in groups L or M (P<0.05).3. In compared with the control group, WT-1positive cells decreased significantly in the group DM.WT-1positive cells obviously increased in PIO and CS treatment groups than in group DM (P<0.05). No significant differences between the treatment groups.4.Compared with the control group, the expression of nephrin was remarkably decreased, the expression of desmin was significantly increased in group DM.The expression of nephrin was obviously increased in PIO or CS treatment groups than in group DM; in group H and PIO,nephrin increased significantly than those in groups L or M. In the treatment groups, desmin decreased significantly than in group DM; in group H and PIO,desmin decreased significantly than those in groups L or M(P<0.05).5. Compared with the group DM, the expression of nephrin mRNA was remarkably increased in the control group, group M、H and PIO,(P<0.05). but there were no significant differences in the treatment groups of DM.Conclusions:1.Our data has shown podocytes decreased significantly, the expression of nephrin was decreased, while the expression of desmin was increased obviously in STZ induced diabetic rats. Podocytes injury could be detected in the early stage of DKD.2. In diabetic rats, the expression of MCP-1was remarkably increased and there was a negative correlation between MCP-1and the number of podocytes or nephrin, a significantly positive correlation between MCP-1and desmin.3.Our data has shown the podocyte protective effect of both CS and PIO on diabetic kidney disease. The mechanisms may be related to inhibit the expression of MCP-l.The renal protective effects seems to be independent of blood glucose control.4.Our data indicated that CS has some dose dependent effects which is cytoprotection for podocytes. |
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